CREPIT, CHU Avicenne, Assistance Publique-Hôpitaux de Paris, Bobigny, France.
Chemotherapy. 2012;58(2):129-33. doi: 10.1159/000337061. Epub 2012 May 10.
The aim of this study was to compare the bactericidal activity of cefepime plus amikacin against experimental pneumonia induced by a stably derepressed cephalosporinase-producing Enterobacter cloacae strain in immunocompetent and leucopenic rats.
Sixty Wistar rats were used. Leucopenia was induced in half of them by a single intravenous administration of 30 mg/kg cyclophosphamide, while the remaining rats received the same volume of saline. All rats were infected 96 h later by tracheal instillation of 8 log(10) colony-forming units of E. cloacae. Twelve rats (6 immunocompetent and 6 leucopenic) were sacrificed 6 h later to assess the initial bacterial burden to the lungs. Then, the remaining 48 rats received a combination of 60 mg/kg cefepime twice a day and 25 mg/kg amikacin once a day given intraperitoneally or the same volume of saline. Six rats per group (leucopenic or not, treated or not) were sacrificed 12 and 30 h after therapy started.
Spontaneous bacterial clearance with time was observed only in immunocompetent rats. Compared to untreated animals, antibiotic administration induced a decrease in lung bacterial titres in immunocompetent and leucopenic rats. The difference was statistically significant only in leucopenic rats.
The use of leucopenic rats reduced spontaneous bacterial clearance in the lungs and increased the bactericidal effect of the antibiotic combination and ultimately the confidence in the reliability of the results.
本研究旨在比较头孢吡肟联合阿米卡星对稳定去阻遏头孢菌素酶产生的阴沟肠杆菌实验性肺炎的杀菌活性，在免疫功能正常和白细胞减少的大鼠中。
使用 60 只 Wistar 大鼠。其中一半大鼠通过单次静脉注射 30mg/kg 环磷酰胺诱导白细胞减少，而其余大鼠给予相同体积的生理盐水。96 小时后，所有大鼠通过气管内滴注 8log10 个菌落形成单位的阴沟肠杆菌进行感染。12 只大鼠（6 只免疫功能正常和 6 只白细胞减少）在 6 小时后被处死，以评估肺部的初始细菌负荷。然后，其余 48 只大鼠接受 60mg/kg 头孢吡肟每天两次和 25mg/kg 阿米卡星每天一次腹腔内给药，或给予相同体积的生理盐水。每组 6 只大鼠（白细胞减少或不，治疗或不）在治疗开始后 12 和 30 小时被处死。
仅在免疫功能正常的大鼠中观察到随时间自发清除细菌。与未治疗动物相比，抗生素治疗可降低免疫功能正常和白细胞减少大鼠肺部的细菌载量。这种差异仅在白细胞减少的大鼠中具有统计学意义。
使用白细胞减少的大鼠减少了肺部的自发清除，并增加了抗生素联合的杀菌效果，最终增加了对结果可靠性的信心。
